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CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse.

Publication ,  Journal Article
Li, Q-J; Dinner, AR; Qi, S; Irvine, DJ; Huppa, JB; Davis, MM; Chakraborty, AK
Published in: Nat Immunol
August 2004

How T cells respond with extraordinary sensitivity to minute amounts of agonist peptide and major histocompatibility complex (pMHC) molecules on the surface of antigen-presenting cells bearing large numbers of endogenous pMHC molecules is not understood. Here we present evidence that CD4 affects the responsiveness of T helper cells by controlling spatial localization of the tyrosine kinase Lck in the synapse. This finding, as well as further in silico and in vitro experiments, led us to develop a molecular model in which endogenous and agonist pMHC molecules act cooperatively to amplify T cell receptor signaling. At the same time, activation due to endogenous pMHC molecules alone is inhibited. A key feature is that the binding of agonist pMHC molecules to the T cell receptor results in CD4-mediated spatial localization of Lck, which in turn enables endogenous pMHC molecules to trigger many T cell receptors. We also discuss broader implications for T cell biology, including thymic selection, diversity of the repertoire of self pMHC molecules and serial triggering.

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Published In

Nat Immunol

DOI

ISSN

1529-2908

Publication Date

August 2004

Volume

5

Issue

8

Start / End Page

791 / 799

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Models, Immunological
  • Mice
  • Major Histocompatibility Complex
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Lymphocyte Activation
  • Immunology
  • Image Processing, Computer-Assisted
 

Citation

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Li, Q.-J., Dinner, A. R., Qi, S., Irvine, D. J., Huppa, J. B., Davis, M. M., & Chakraborty, A. K. (2004). CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse. Nat Immunol, 5(8), 791–799. https://doi.org/10.1038/ni1095
Li, Qi-Jing, Aaron R. Dinner, Shuyan Qi, Darrell J. Irvine, Johannes B. Huppa, Mark M. Davis, and Arup K. Chakraborty. “CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse.Nat Immunol 5, no. 8 (August 2004): 791–99. https://doi.org/10.1038/ni1095.
Li Q-J, Dinner AR, Qi S, Irvine DJ, Huppa JB, Davis MM, et al. CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse. Nat Immunol. 2004 Aug;5(8):791–9.
Li, Qi-Jing, et al. “CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse.Nat Immunol, vol. 5, no. 8, Aug. 2004, pp. 791–99. Pubmed, doi:10.1038/ni1095.
Li Q-J, Dinner AR, Qi S, Irvine DJ, Huppa JB, Davis MM, Chakraborty AK. CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse. Nat Immunol. 2004 Aug;5(8):791–799.

Published In

Nat Immunol

DOI

ISSN

1529-2908

Publication Date

August 2004

Volume

5

Issue

8

Start / End Page

791 / 799

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Models, Immunological
  • Mice
  • Major Histocompatibility Complex
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Lymphocyte Activation
  • Immunology
  • Image Processing, Computer-Assisted